DESCRIPTION (Taken from the applicant's Abstract) Chronic non-infectious prostatitis or chronic pelvic pain syndrome (CPPS) represents one of the greatest challenges in clinical medicine. It consists of a constellation of symptoms that are subjectively evaluated by both the patient and his physician. These may include perineal and thigh pain, penile discomfort, orchalgia, lower back pain, irritative and obstructive voiding symptoms, ejaculatory dysfunction, fatigue, and a variety of other complaints. Treatments often lead to minimal or intermittent improvement, frequent exacerbations, increasing frustration, and extensive utilization of resources. In CPPS, physicians and researchers lack a clear understanding of the relevant pathophysiology and immunology, lack consensus on what constitutes the appropriate diagnostic evaluation and therapeutic management, and disagree on how best to quantify patients' symptoms and the resulting quality of life impact. The goal of this proposal is to carry out two specific projects that address current knowledge deficits in CPPS. The first involves the development and validation of a symptom index and a quality of life impact index for men with CPPS. The multi-center nature of the project will allow for the creation of an instrument that is psychometrically reliable and valid yet easily understood and completed by patients. With a uniformly accepted outcome measure, researchers and clinicians can begin speaking the same language when assessing the natural history of this disease and its response to various proposed treatments. The second is to determine whether CPPS is an inappropriate injury response in the absence of ongoing bacterial injury. It will establish signal modulators that provide novel and effective tools to diagnose CPPS and to select and monitor treatment efficacy for individual patients. We will study the biochemical, cellular and molecular markers from the fluid and cells of expressed prostatic secretions and correlate these parameters with the outcomes measures developed in the first project. The biological measures will include quantification of white blood cells, nitric oxide activity in prostatic fluid, and fluorescent in situ hybridization of prostate fluid cells for markers of individual immune cell types and immune cell activation.